LncRNA HCP5 promotes LAML progression via PSMB8-mediated PI3K/AKT pathway activation.

Acute myeloid leukemia is an aggressive myeloid malignancy, characterized by rapid cellular proliferation and generally high mortality. Due to the lack of a complete understanding of AML, its clinical outcomes are still not satisfactory. In this study, we examined the function of the long non-coding RNA-HLA complex P5 (HCP5) on AML by analyzing the clinical samples, TCGA data, and by shRNA-mediated HCP5 deficiency in vitro. Our results showed that HCP5 is highly expressed in AML and is positive associated with poor prognosis, and HCP5 knockdown was significantly suppressing AML cell line proliferation and inducing G1/S arrest in vitro. In mechanism, the proteasome subunit beta type 8 (PSMB8) expression was dramatically inhibited in HCP5 knockdown cells while increased in HCP5 overexpression cells. PSMB8 was also highly expressed in AML and with poor prognosis. Furthermore, HCP5 regulates PI3K/AKT pathway activation depending on PSMB8. Our results showed a promoting function of HCP5 on AML and may provide a compelling biomarker and therapy target for AML.

A clinical study of allogeneic hematopoietic stem cell transplantation in 23 patients with early T-cell precursor acute lymphoblastic leukemia / 中华血液学杂志

Objective@#Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a recently recognized high-risk T lymphoblastic leukemia subgroup. The optimal therapeutic approaches to adult patients with ETP-ALL are poorly characterized. In this study, we explore the efficacy and outcome of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ETP-ALL.@*Methods@#The clinical data of 23 patients with ETP-ALL receiving allo-HSCT from 2010 to 2018 were retrospectively analyzed. Patients with ETP-ALL were diagnosed based on the characteristic immunophenotypes. Second-generation sequencing was done in all patients. As to the donors, 12 patients had haploidentical donors (Haplo-HSCT) , 7 HLA-matched sibling donors (Sib-HSCT) and 4 HLA-matched unrelated donors (URD-HSCT) . Before transplantation, 19 patients achieved complete remission (CR) and 4 patients without.@*Results@#The main clinical features of ETP-ALL included high white blood cell counts in 5 patients, splenomegaly in 14, lymphadenopathy in 19, and thymus masses in 5. According to cytogenetic and molecular characteristics, 11 patients had gene mutations related to myeloid tumors, and 7 with high risk Karyotype. After first induction regimen, 14/23 patients achieved CR. 5 patients reached CR after more than 2 cycles of chemotherapy, while another 4 patients did not reach CR. After allo-HSCT, 22 patients were successfully implanted. The median time of granulocyte and platelet reconstitution was +12 and +19 days. One patient died of transplant-related infection at +14 days. The estimated 18-month overall survival (OS) and relapse-free survival (RFS) rates were (55.0±14.4) % and (48.1±14.7) % respectively. Transplant-related mortality was 4.3%. The median OS in patients achieving CR before transplantation was 20 months, however, that in patients without CR was only 13 months. OS and RFS between haplo-HSCT and sib-HSCT were comparable (P=0.460 and 0.420 respectively) .@*Conclusions@#Allo-HSCT is an effective therapy in some patients with ETP-ALL. Salvage HSCT cannot overcome the poor outcome. Haplo-HSCT and sib-HSCT in ETP-ALL patients have the similar clinical outcome.